Biology subjects
Publications and source records attributed to Duarte, T. L..
Patient-derived xenografts (PDX) are valuable tools to model human disease and test new therapies. Here, we report, for the first time, a PDX model recapitulating the unique characteristics of a VEXAS patient (unique patient number UPN1).
Malaria and iron deficiency are major global health problems with extensive epidemiological overlap. Iron deficiency-induced anaemia can protect the host from malaria by limiting parasite growth. On the other hand, iron deficiency can significantly disrupt immune cell function. However, the impact of host cell iron scarcity beyond anaemia remains elusive in malaria. To address this, we employed a transgenic mouse model carrying a mutation in the transferrin receptor (TfrcY20H/Y20H), which limits the ability of cells to internalise iron from plasma. At homeostasis TfrcY20H/Y20H mice appear healthy and are not anaemic. However, TfrcY20H/Y20H mice infected with Plasmodium chabaudi chabaudi AS showed significantly higher peak parasitaemia and body weight loss. We found that TfrcY20H/Y20H mice displayed a similar trajectory of malaria-induced anaemia as wild-type mice, and elevated circulating iron did not increase peak parasitaemia. Instead, P. chabaudi infected TfrcY20H/Y20H mice had an impaired innate and adaptive immune response, marked by decreased cell proliferation and cytokine production. Moreover, we demonstrated that these immune cell impairments were cell-intrinsic, as ex vivo iron supplementation fully recovered CD4 T cell and B cell function. Despite the inhibited immune response and increased parasitaemia, TfrcY20H/Y20H mice displayed mitigated liver damage, characterised by decreased parasite sequestration in the liver and an attenuated hepatic immune response. Together, these results show that host cell iron scarcity inhibits the immune response but prevents excessive hepatic tissue damage during malaria infection. These divergent effects shed light on the role of iron in the complex balance between protection and pathology in malaria.
The red macroalgae (seaweed) Asparagopsis spp. has shown to reduce ruminant enteric methane (CH4) production up to 99% in vitro. The objective of this study was to determine the effect of Asparagopsis taxiformis on CH4 production (g/day per animal), CH4 yield (g CH4/kg dry matter intake (DMI)), average daily gain (ADG), feed conversion efficiency (FCE), and carcass and meat quality in growing beef steers. Twenty-one Angus-Hereford beef steers were randomly allocated to one of three treatment groups: 0% (Control), 0.25% (Low Dose; LD), and 0.5% (High Dose; HD) A. taxiformis inclusion based on organic matter intake. Steers were fed 3 diets: high, medium, and low forage total mixed ration (TMR) representing typical life-stage diets of growing beef steers. The LD and HD treatments over 147 days reduced enteric CH4 yield 45 and 68%, respectively; however, there was an interaction between TMR type and the magnitude of CH4 yield reduction. Supplementing the low forage TMR reduced CH4 yield 69.8% (P <0.001) for LD and 80% (P <0.001) for HD treatment. Hydrogen (H2) yield (g H2/DMI) increased significantly (P<0.001) 336 and 590% compared to Control for the LD and HD treatments, respectively. No differences were found in carbon dioxide (CO2) yield (g CO2/DMI), ADG, carcass quality, strip loin proximate analysis and shear force, or consumer taste preferences. DMI tended (P = 0.08) to decrease 8% in steers in LD treatment but significantly (P = 0.002) reduced 14% in steers in HD treatment. Conversely, FCE tended to increase 7% in steers in LD treatment (P = 0.06) and increased 14% in steers in HD (P < 0.01) treatment compared to Control. The persistent reduction of CH4 by A. taxiformis supplementation suggests that this is a viable feed additive to significantly decrease the carbon footprint of ruminant livestock and potentially increase production efficiency.